The etiology of most Parkinson's disease is unknown. Recent research suggests that the disease may in part be caused by exposure to an environmental toxin. Proof that any environmental agent is capable of initiating Parkinson's disease would lend strong support to this hypothesis. Horses that eat plants of the species Centaurea solstitialis have been reported to develop brain lesions in similar neuroanatomical regions as is found in Parkinson's disease. The aims of this research are 1) to isolate and determine the structure of the neurotoxin in Centaurea solstitialis; 2) to compare the effects of the isolated agent to the known neurotoxin in MPTP; and 3) to assess the mechanism of action of the toxic agent and determine its relationship to the occurrence of neurodegenerative diseases. Centaurea solstitialis will be collected and the compounds contained in the plant will be extracted and purified. Constituents of the plant will be assayed in a frog and/or a mouse model for toxicity to dopaminergic neurons. When the toxic agent in the plant has been identified, its chemical structure will be determined by NMR and mass spectroscopic techniques. Studies into the mechanism of action of the plant neurotoxin will be conducted and compared to the known neurotoxin MPTP. The research will attempt to evaluate the potential of human exposure to this environmental toxin to cause neurodegenerative diseases.